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N-Glycans in the gp120 V1/V2 domain of the HIV-1 strain NL4-3 are indispensable for viral infectivity and resistance against antibody neutralization

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Abstract

Here we report that N-glycans within the V1/V2 variable regions of the NL4-3 gp120 glycoprotein are indispensable to maintain viral functionality and are masking neutralizing epitopes. Fifteen variants of HIV-1 isolate NL4-3 with mutations of the six N-glycosylation sites g2–g7 within the V1 (g2–g4) and V2 loop (g5–g7) of gp120 were analyzed for viral infectivity and their sensitivity to neutralization. Presence of the N-glycans g4, g5, g6 and g7 was an important prerequisite to maintain viral infectivity, since virus mutants lacking these N-glycans were highly deficient in virus entry. Lack of g4 or g7 correlated to a reduction of infectivity to less than 3% of the infectivity observed for NL4-3 wild type. In contrast, mutants lacking N-glycans g2 and g3 showed a 50% increase in infectivity compared to NL4-3. Mutants lacking g2, g3, g5 and g6 with an infectivity of more than 10% of the NL4-3 wt virus were tested for neutralization and showed a high sensitivity against human serum antibody from HIV-1 infected individuals.

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Acknowledgment

This work was supported in parts by a grant to M.S. from the Deutsche Forschungsgemeinschaft by SFB 470 and GRK 464.

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  1. Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Str. 74, 20359, Hamburg, Germany

    Tobias Wolk & Michael Schreiber

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  1. Tobias Wolk
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Correspondence to Michael Schreiber.

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Wolk, T., Schreiber, M. N-Glycans in the gp120 V1/V2 domain of the HIV-1 strain NL4-3 are indispensable for viral infectivity and resistance against antibody neutralization. Med Microbiol Immunol 195, 165–172 (2006). https://doi.org/10.1007/s00430-006-0016-z

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